R5.4b: Classes Of Damage

Damage inflicted to the cell is classed into three categories: Lethal damage, sublethal damage and potentially lethal damage.

Lethal Damage

Lethal damage is damage that is so widespread or complex that the cell is unable to repair the problem.

Sublethal Damage

This is a more interesting type of damage. Sublethal damage was discovered when a single radiation dose was instead given as two split doses. The number of cells that died from the split dose was less than the single large dose. This implied that some of the damage was repaired between the fractions.
The ability of cells to repair themselves between doses of radiation implies that repair mechanisms can protect cells against some part of the radiation. This is important for normal tissues, which will usually have preserved repair pathways.

Timing of repair

The amount of repair occuring follows an exponential curve and has a half life (the time for half of the damage to be repaired). For tissues in culture, the repair half life is about 1 hour. Some in vivo tissues have several repair half lives, probably representing different DNA repair pathways. For example, the spinal cord shows a component of rapid repair (with a half life of 15 minutes) and a longer repair process (with a half life of about 3 - 5 hours). This is important when delivering more than one fraction per day - sufficient time must be left between fractions to allow these slower repair pathways to work.

Potentially Lethal Damage

Potentially lethal damage is damage that can be repaired under certain conditions, such as the presence of favourable environmental features or cell cycle arrest. If cells are in S-phase, they are readily able to repair DNA damage. If cells are in M-phase, DNA damage can not be repaired as there are numerous other cellular processes in action.
Tumour cells, which have defective cell cycle controls, may be unable to arrest their progression through the cycle (and into M-phase and mitotic catastrophe). This is another potential way the difference between tumours and normal tissues can be exploited.